Autism is a severe neurobiological condition with a strong genetic component that presents in early childhood. Several structural brain abnormalities have been associated with autism, though none have been consistently replicated and no single abnormality is seen in all persons with autism. A possible reason for these inconsistencies is the difficulty of controlling the genetic and environmental variables that can alter brain morphology. In this study, we propose to investigate cortical complexity in siblings discordant for autism. This study population will allow us to gain greater experimental control of genetic and environmental factors that influence brain development. We plan to use a novel, whole-brain analysis of cortical complexity to assess the relation between cortical brain morphology and autism in a sample of 27 same-gender sibling- pairs discordant for autism, as well as in 27 typically developing participant who are age- and gender- matched to the siblings of participants with autism. In addition, we propose to assess the relation between cortical folding complexity and behavioral features of autistic participants. Finally, by comparing results with a younger sample of 19 children with autism and 13 age-matched controls (17-40 months of age), we will be able to assess the developmental trajectory of cortical folding complexity in autism from the second year of life to 12 years of age. We hypothesize that brain regions important for social cognition, communication, and face recognition will be altered in autism as compared to their unaffected siblings and controls. In addition, we hypothesize that abnormal shape morphology in these regions will be correlated with the severity of social and communication impairments in participants with autism. We further hypothesize that development of cortical folding complexity (change of shape with age) will be altered between the second year of life and 12 years of age in participants with autism as compared to the control groups. This information will help to specify which neuroanatomical regions are indeed associated with autism, and how they develop throughout childhood. PUBLIC HEALTH RELEVANCE: Although autism is well recognized as a neurobiological condition, the specific neurodevelopmental pathways leading to the cognitive and behavioral disturbances in autism are unknown. In the proposed study, we will use novel neuroimaging techniques to begin to define meaningful biological sub-divisions of autism. A better understanding of the neurobiological underpinning of autism will allow to identify sub-groups of individuals with autism, leading to the development of more targeted treatments for this disorder.